Skip to Main Content

Essentials of Diagnosis

  • Diagnosis by positive anti–hepatitis C virus (HCV) antibody confirmed by a sensitive, qualitative HCV RNA assay.
  • Arthralgias and rarely a nonerosive arthritis are seen in patients with chronic HCV infection, with or without associated cryoglobulinemia.
  • Coexistent rheumatoid arthritis (RA) and HCV infection can create diagnostic and therapeutic problems.

General Considerations

Chronic hepatitis C is second only to hepatitis B (see next section) among the common chronic viral infection worldwide, with an estimated 170 million people infected. In the United States, chronic HCV infection affects 4.1 million people, represents the leading cause of liver transplantation and death from liver disease, and has surpassed HIV infection as a cause of death.

HCV, an RNA virus, is transmitted by the parenteral route. The most common causes of HCV transmission are injection drug use and transfusion of blood or blood-derived products before 1992. Infrequent modes of transmission include accidental exposures at work (eg, health care workers), sex, and childbirth. In a number of cases, no identifiable risk factor can be found. There is currently no vaccine available for HCV. Screening of blood products has almost eliminated the risk of post-transfusion hepatitis C. The persons at greatest risk for HCV now are injection drug users and persons with high-risk sexual behavior (multiple sexual partners).

Less than 20% of patients with acute HCV infections are symptomatic at the time of infection. Most cases of HCV, however, are associated with transition to chronicity (55–85%). The natural history of chronic HCV infection is variable. Between 5% and 20% of chronically infected HCV patients develop cirrhosis within several decades. Among cirrhotic patients, within 10 years 30% develop end-stage liver disease and 10–20% develop hepatocellular carcinoma. Factors associated with more rapid disease progression include older age, alcohol abuse, coinfection with HIV (see Chapter 51), and the presence of hepatic steatosis.

Chronic HCV infection is uniquely associated with a number of extrahepatic rheumatic manifestations including arthralgias, arthritis, sialadenitis (Sjögren-like), and cryoglobulinemic vasculitis.


HCV replicates predominantly in hepatocytes after entrance into the circulation. Following acute infection, HCV RNA can be detected in the serum within 1 week. Alanine aminotransferase elevation occurs 2–3 months later. Anti-HCV antibodies can be found 1–2 months after acute infection. Acute HCV infection is not associated with rheumatic complaints (in contrast to acute hepatitis B), and many patients do not know that they are infected.

HCV exhibits tropism for hepatocytes, B lymphocytes, and salivary and lachrymal gland epithelial cells. Monoclonal and polyclonal B-cell expansions have been found in the liver and bone marrow of chronically infected patients. In approximately half of patients with chronic HCV infections, circulating cryoglobulins can be detected. However, only a minority of these patients (<5%) develop the syndrome of mixed cryoglobulinemia (see Chapter 36). Deposition of immune complexes containing cryoglobulins in different ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.